Purpose Three related male English Cocker Spaniels (ECS) were reported to be congenitally blind. Examination of one of these revealed complete retinal detachment. A presumptive diagnosis of retinal dysplasia (RD) was provided and pedigree analysis was suggestive of an X-linked mode of inheritance. We sought to investigate the genetic basis of RD in this family of ECS. Methods Following whole genome sequencing (WGS) of the one remaining male RD-affected ECS, two distinct investigative approaches were employed: a candidate gene approach and a whole genome approach. In the candidate gene approach, COL9A2, COL9A3, NHEJ1, RS1 and NDP genes were investigated based on their known associations with RD and retinal detachment in dogs and humans. In the whole genome approach, affected WGS was compared with 814 unaffected canids to identify candidate variants, which were filtered based on appropriate segregation and predicted pathogenic effects followed by subsequent investigation of gene function. Candidate variants were tested for appropriate segregation in the ECS family and association with disease was assessed using samples from a total of 180 ECS. Results The same variant in NDP (c.653_654insC, p.Met114Hisfs*16) that was predicted to result in 15 aberrant amino acids before a premature stop in norrin protein, was identified independently by both approaches and was shown to segregate appropriately within the ECS family. Association of this variant with X-linked RD was significant (P = 0.0056). Conclusions For the first time, we report a variant associated with canine X-linked RD. NDP variants are already known to cause X-linked RD, along with other abnormalities, in human Norrie disease. Thus, the dog may serve as a useful large animal model for research.

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Objective We hypothesized that keratouveitis still occurs despite current widespread use of Canine adenovirus (CAV)‐2 vaccinations and assessed the utility of CAV‐1 and CAV‐2 titers in elucidation of its etiopathogenesis. Animals studied Nine dogs with unexplained keratouveitis (14 eyes) and nine control dogs. Procedures The Animal Health Trust clinical database was searched between 2008 and 2018 to identify cases of keratouveitis. Inclusion criteria included known vaccination status, interval from vaccination to development of clinical signs and availability of CAV titers. Cases were excluded if they were older than 1 year of age, or other causative ocular pathology for corneal edema was identified. Nine age‐matched dogs without corneal edema but with CAV titers were included as controls. Results Mean CAV‐1 and CAV‐2 titers were not statistically different between dogs with keratouveitis and controls (p = .16 and p = .76, respectively). Three cases had CAV‐1 titers >5000 and two of these cases had rising convalescence titers (greater than an 11‐fold increase) suggesting infection with wild‐type CAV‐1. The six other cases did not appear to be associated with CAV infection or vaccination. Conclusion Keratouveitis continues to occur despite the advent of CAV‐2 vaccinations. While this study found no evidence to indicate CAV‐2 vaccination causes keratouveitis, the data indicates that in a proportion of cases, contemporaneous wild‐type CAV‐1 infection is a possible cause.